Fig. 4. Age stratified serosurveys provide important clues to local ZIKV epidemiology.

Results must be interpreted with caution bacuse of the possibility of cross-reactivity with other flavivirus antibodies. (A–C) Ongoing ZIKV transmission, whether from endemic human transmission or a constant risk of zoonotic infection, manifests as a smooth increase in the proportion of the population seropositive with increasing age. This pattern is also consistent with frequent reintroductions leading to periodic outbreaks. If we assume that the risk of ZIKV infection is constant over a lifetime, we can estimate the force of infection (FOI): the proportion of the susceptible population infected each year. Serosurvey results consistent with ongoing transmission include: (A) Uburu, Nigeria, 1952 (13), (B) Central African Republic, 1979 (pink=female, red=male) (118), and (C) Malaysia, 1953–54 (16). Blue dashed lines and text represent the expected trajectory from the estimated FOI. (D–E) In areas without significant ZIKV transmission there will be very low levels of seropositivity across age groups, and no clear age pattern. Some individuals may still be seropositive due to cross-reactivity in serological assays, infection of travelers, and limited imported cases. Examples include (D) Central Nyanza, Kenya, 1966–1968 (121) and (E) Mid-Western Region, Nigeria, 1966–1967 (120). (F) Significant shifts in seropositivity between age groups inconsistent with ongoing transmission suggest past epidemics, e.g., results from a 1966–1968 serosurvey in the Malindi district of Kenya are consistent with one or more epidemics of ZIKV occurring 15–30 years prior (121). Similar patterns could also occur due to differences in infection risk by age or a sharp reduction in transmission intensity at some point in the past.